Independent discoveries in this laboratory and Canberra of normally occurring transmission failure in the central projections of Ia fibers to motoneurons raise many questions about the incidence, nature and significance of this previously unsuspected phenomenon in the C.N.S. of healthy individuals and its possible accentuation in disease. The long term objectives of this proposal are 1) to define which monocynaptic connections of the Ia-motoneuron projections of normal cats are most susceptible to failure, i.e., which morphological and topographical factors predispose to it, 2) to determine the incidence of failure, 3) to identify the exact site where it occurs and 4) to learn how failure is relieved. Methods have already been developed and preliminary results obtained. A greatly expanded version of spike-triggered averaging performed off-line on taped signals will be used to record single-fiber EPSPs elicited in 10-20 motoneurons by impulses in 10-20 afferent fibers. The aim is to study 100-300 combinations with known anatomical connections in each experiment and, thus, to determine the presence or absence of functional connections between them. Wiring diagrams will be constructed (see Fig. 1) showing the locations of connections where failure is complete for comparison with those where EPSPs were evoked. Connectivity matrices will be assembled (Fig. 2) to display how transmission failure is correlated with the axonal conduction velocities of afferent fibers and motoneurons (i.e., their sizes) and with the distances between motoneurons and spinal entry levels of afferent fibers (preliminary findings indicate significant correlations). The "shape-indices" of the EPSPs (rise times and half-widths) will be used to compute the locations of the active synapses on the motoneurons. Similarly, locations of synapses that fluctuate between silence and activity will be determined. The data should reveal the extent to which morphological factors correlated with transmission failure are expressed in cell-to-cell relations. Indirect evidence from posttetanic potentiation (P.T.P.) suggests that transmission failure occurs to some degree at almost all Ia-motoneuron junctions. P.T.P. will be used to disclose the presence of inactive synapses among the active ones. Increases in the amplitude and/or changes in shape of control EPSPs during P.T.P. would indicate that previously inactive synapses had become active. Locations of such "silent" synapses would be computed from the shape-indices of the newly elicted components of the EPSPs.